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https://www.readbyqxmd.com/read/28925524/hypothermia-increases-aquaporin-4-aqp4-plasma-membrane-abundance-in-human-primary-cortical-astrocytes-via-a-calcium-transient-receptor-potential-vanilloid-4-trpv4-and-calmodulin-mediated-mechanism
#1
Mootaz M Salman, Philip Kitchen, M Nicola Woodroofe, James E Brown, Roslyn M Bill, Alex C Conner, Matthew T Conner
Human aquaporin 4 (AQP4) is the primary water channel protein in brain astrocytes. Hypothermia is known to cause astrocyte swelling in culture, but the precise role of AQP4 in this process is unknown. Primary human cortical astrocytes were cultured under hypothermic (32°C) or normothermic (37°C) conditions. AQP4 transcript, total protein and surface localized protein were quantified using RT-qPCR, sandwich ELISA with whole cell lysates, or cell-surface biotinylation followed by ELISA analysis of the surface-localized protein, respectively...
September 19, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28924972/targeting-nociceptive-trp-channels-to-treat-chronic-pain-current-state-of-the-field
#2
REVIEW
Magdalene M Moran, Arpad Szallasi
Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of Transient Receptor Potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically...
September 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28924052/role-of-the-endothelial-caveolae-microdomain-in-shear-stress-mediated-coronary-vasorelaxation
#3
Tong Lu, Xiao-Li Wang, Qiang Chai, Xiaojing Sun, Gary C Sieck, Zvonimir S Katusic, Hon-Chi Lee
In this study, we determined the role of caveolae and the ionic mechanisms that mediate shear stress-mediated vasodilation (SSD). We found that both TRPV4 and SK channels are targeted to caveolae in freshly isolated bovine coronary endothelial cells (BCECs) and that TRPV4 and KCa2.3 (SK3) channels are co-immunoprecipitated by anti-caveolin-1 antibodies. Acute exposure of BCECs seeded in a capillary tube to 10 dynes/cm2 of SS resulted in activation of TRPV4 and SK currents. However, after incubation with HC067047 (TRPV4 inhibitor) SK currents could no longer be activated by SS, suggesting SK channel activation by SS was mediated through TRPV4...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28922668/activation-of-trpv4-increases-neovascularization-of-rat-prefabricated-flaps
#4
Jinhong Bae, Zhichao Wang, Haizhou Li, Lin Lu, Qingxiong Yu, Qingfeng Li, Zan Tao
No abstract text is available yet for this article.
September 18, 2017: Journal of Reconstructive Microsurgery
https://www.readbyqxmd.com/read/28902413/frequent-genes-in-rare-diseases-panel-based-next-generation-sequencing-to-disclose-causal-mutations-in-hereditary-neuropathies
#5
Maike F Dohrn, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Julia Mohr, Christine Bauer, Erik Riesch, Andrea Becker, Florian Battke, Konstanze Hörtnagel, Thorsten Hornemann, Saranya Suriyanarayanan, Markus Blankenburg, Jörg B Schulz, Kristl G Claeys, Burkhard Gess, Istvan Katona, Andreas Ferbert, Debora Vittore, Alexander Grimm, Stefan Wolking, Ludger Schöls, Holger Lerche, G Christoph Korenke, Dirk Fischer, Bertold Schrank, Urania Kotzaeridou, Gerhard Kurlemann, Bianca Dräger, Anja Schirmacher, Peter Young, Beate Schlotter-Weigel, Saskia Biskup
Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing (NGS) technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Out of these, 54.4% showed an autosomal dominant, 33...
September 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28899928/treatment-of-hypertension-by-increasing-impaired-endothelial-trpv4-kca2-3-interaction
#6
Dongxu He, Qiongxi Pan, Zhen Chen, Chunyuan Sun, Peng Zhang, Aiqin Mao, Yaodan Zhu, Hongjuan Li, Chunxiao Lu, Mingxu Xie, Yin Zhou, Daoming Shen, Chunlei Tang, Zhenyu Yang, Jian Jin, Xiaoqiang Yao, Bernd Nilius, Xin Ma
The currently available antihypertensive agents have undesirable adverse effects due to systemically altering target activity including receptors, channels, and enzymes. These effects, such as loss of potassium ions induced by diuretics, bronchospasm by beta-blockers, constipation by Ca(2+) channel blockers, and dry cough by ACEI, lead to non-compliance with therapies (Moser, 1990). Here, based on new hypertension mechanisms, we explored a new antihypertensive approach. We report that transient receptor potential vanilloid 4 (TRPV4) interacts with Ca(2+)-activated potassium channel 3 (KCa2...
September 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28898540/compound-heterozygous-trpv4-mutations-in-two-siblings-with-a-complex-phenotype-including-severe-intellectual-disability-and-neuropathy
#7
My Linh Thibodeau, Colin H Peters, Katelin N Townsend, Yaoqing Shen, Glenda Hendson, Shelin Adam, Kathryn Selby, Patrick M Macleod, Cynthia Gershome, Peter Ruben, Steven J M Jones, Jan M Friedman, William T Gibson, Gabriella A Horvath
TRPV4 encodes a polymodal calcium-permeable plasma membrane channel. Dominant pathogenic mutations in TRPV4 lead to a wide spectrum of abnormal phenotypes. This is the first report of biallelic TRPV4 mutations and we describe two compound heterozygous siblings presenting with a complex phenotype including severe neuromuscular involvement. In light of previously well described dominant inheritance for TRPV4-related neuromuscular disease, our study suggests a role for compound heterozygosity and loss-of-function as a potential novel disease mechanism for this group of disorders...
September 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884838/review-article-transient-receptor-potential-channels-as-possible-therapeutic-targets-in-irritable-bowel-syndrome
#8
REVIEW
A B Beckers, Z Z R M Weerts, Z Helyes, A A M Masclee, D Keszthelyi
BACKGROUND: Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well...
September 8, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28881406/the-circadian-expression-of-piezo1-trpv4-connexin26-and-vnut-associated-with-the-expression-levels-of-the-clock-genes-in-mouse-primary-cultured-urothelial-cells
#9
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Mie Kanda, Sachiko Tsuchiya, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
AIMS: To investigate circadian gene expressions in the mouse bladder urothelium to establish an experimental model and study the functions of the circadian rhythm. METHODS: The gene expression rhythms of the clock genes, mechano-sensors such as Piezo1 and TRPV4, ATP release mediated molecules (ARMM) such as Cx26 and VNUT were investigated in mouse primary cultured urothelial cells (UCs) of wild-type (WT) and Clock mutant (Clock(Δ19)(/Δ)(19) ) mice using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting analysis...
September 7, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28874838/structural-determinants-of-5-6-epoxyeicosatrienoic-acid-binding-to-and-activation-of-trpv4-channel
#10
Alejandro Berna-Erro, Mercè Izquierdo-Serra, Romina V Sepúlveda, Fanny Rubio-Moscardo, Pau Doñate-Macián, Selma A Serra, Julia Carrillo-Garcia, Alex Perálvarez-Marín, Fernando González-Nilo, José M Fernández-Fernández, Miguel A Valverde
TRPV4 cation channel activation by cytochrome P450-mediated derivatives of arachidonic acid (AA), epoxyeicosatrienoic acids (EETs), constitute a major mechanisms of endothelium-derived vasodilatation. Besides, TRPV4 mechano/osmosensitivity depends on phospholipase A2 (PLA2) activation and subsequent production of AA and EETs. However, the lack of evidence for a direct interaction of EETs with TRPV4 together with claims of EET-independent mechanical activation of TRPV4 has cast doubts on the validity of this mechanism...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867591/heteromeric-trpv4-trpc1-channels-mediate-calcium-sensing-receptor-induced-nitric-oxide-production-and-vasorelaxation-in-rabbit-mesenteric-arteries
#11
Harry Z E Greenberg, Simonette R E Carlton-Carew, Dhanak M Khan, Alexander K Zargaran, Kazi S Jahan, W-S Vanessa Ho, Anthony P Albert
Stimulation of calcium-sensing receptors (CaSR) by increasing the external calcium concentration (Ca(2+)]o) induces endothelium-dependent vasorelaxation through nitric oxide (NO) production and activation of intermediate Ca(2+)-activated K(+) currents (IKCa) channels in rabbit mesenteric arteries. The present study investigates the potential role of heteromeric TRPV4-TRPC1 channels in mediating these CaSR-induced vascular responses. Immunocytochemical and proximity ligation assays showed that TRPV4 and TRPC1 proteins were expressed and co-localised at the plasma membrane of freshly isolated endothelial cells (ECs)...
September 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28863406/a-role-for-calcium-activated-adenylate-cyclase-and-protein-kinase-a-in-the-lens-src-family-kinase-and-na-k-atpase-response-to-hyposmotic-stress
#12
Mohammad Shahidullah, Amritlal Mandal, Nicholas A Delamere
Purpose: Na,K-ATPase activity in lens epithelium is subject to control by Src family tyrosine kinases (SFKs). Previously we showed hyposmotic solution causes an SFK-dependent increase in Na,K-ATPase activity in the epithelium. Here we explored the role of cAMP in the signaling mechanism responsible for the SFK and Na,K-ATPase response. Methods: Intact porcine lenses were exposed to hyposmotic Krebs solution (200 mOsm) then the epithelium was assayed for cAMP, SFK phosphorylation (activation) or Na,K-ATPase activity...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28859335/a-new-mutation-in-fig4-causes-a-severe-form-of-cmt4j-involving-trpv4-in-the-pathogenic-cascade
#13
Benoit J Gentil, Erin O'Ferrall, Colin Chalk, Luis F Santana, Heather D Durham, Rami Massie
Mutations in FIG4, coding for a phosphoinositol(3,5) bisphosphate 5' phosphatase and involved in vesicular trafficking and fusion, have been shown causing a recessive form of Charcot-Marie-Tooth (CMT). We have identified a novel intronic mutation in the FIG4 in a wheel-chair bound patient presenting with a severe form of CMT4J and provide a longitudinal study. Investigations indicated a demyelinating sensorimotor polyneuropathy with diffuse active denervation and severe axonal loss. Genetic testing revealed that the patient is heterozygous for 2 FIG4 mutations, p...
September 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28856727/cholesterol-regulates-polymodal-sensory-transduction-in-m%C3%A3-ller-glia
#14
Monika Lakk, Oleg Yarishkin, Jackson M Baumann, Anthony Iuso, David Križaj
Over- and underexposure to cholesterol activates glia in neurodegenerative brain and retinal diseases but the molecular targets of cholesterol in glial cells are not known. Here, we report that disruption of unesterified membrane cholesterol content modulates the transduction of chemical, mechanical and temperature stimuli in mouse Müller cells. Activation of TRPV4 (transient receptor potential vanilloid type 4), a nonselective polymodal cation channel was studied following the removal or supplementation of cholesterol using the methyl-beta cyclodextrin (MβCD) delivery vehicle...
August 30, 2017: Glia
https://www.readbyqxmd.com/read/28853179/hyperosmolarity-induces-notochordal-cell-differentiation-with-aquaporin3-upregulation-and-reduced-n-cadherin-expression
#15
Paolo E Palacio-Mancheno, Thomas W Evashwick-Rogler, Damien M Laudier, Devina Purmessur, James C Iatridis
The nucleus pulposus (NP) of intervertebral discs (IVD) undergoes dramatic changes with aging including loss of its gelatinous structure and large, vacuolated notochordal cells (NCs) in favor of a matrix-rich structure populated by small NP cells (sNPCs). NP maturation also involves a loading-pattern shift from pressurization to matrix deformations, and these events are thought to predispose to degeneration. Little is known of the triggering events and cellular alterations involved with NP maturation, which remains a fundamental open spinal mechanobiology question...
August 29, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#16
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807414/transient-receptor-potential-vanilloid-4-expressing-macrophages-and-keratinocytes-contribute-differentially-to-allergic-and-nonallergic-chronic-itch
#17
Jialie Luo, Jing Feng, Guang Yu, Pu Yang, Madison R Mack, Junhui Du, Weihua Yu, Aihua Qian, Yujin Zhang, Shenbin Liu, Shijin Yin, Amy Xu, Jizhong Cheng, Qingyun Liu, Roger G O'Neil, Yang Xia, Liang Ma, Susan M Carlton, Brian S Kim, Kenneth Renner, Qin Liu, Hongzhen Hu
BACKGROUND: Chronic itch is a highly debilitating symptom that underlies many medical disorders with no universally effective treatments. Although unique neuronal signaling cascades in the sensory ganglia and spinal cord have been shown to critically promote the pathogenesis of chronic itch, the role of skin-associated cells remains poorly understood. OBJECTIVE: We sought to examine the cutaneous mechanisms underlying transient receptor potential vanilloid 4 (TRPV4)-mediated allergic and nonallergic chronic itch...
August 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28790335/involvement-of-transient-receptor-potential-cation-channel-member-a1-activation-in-the-irritation-and-pain-response-elicited-by-skin-lightening-reagent-hydroquinone
#18
Yan Tai, Chuan Wang, Zhihua Wang, Yi Liang, Junying Du, Dongwei He, Xiaoyan Fan, Sven-Eric Jordt, Boyi Liu
Hydroquinone (HQ) is one of the most frequently used and effective skin-lightening products to treat skin hyperpigmentation disorders, including postinflammatory hyperpigmentation, melasma and solar lentigines. HQ is also widely used in cosmetic products for skin whitening. However, HQ treatment can evoke substantial skin irritation, a side effect that remains poorly understood. Here we demonstrate that HQ is an activator of the peripheral irritant receptor transient receptor potential (TRP) cation channel member A1 (TRPA1)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768667/trpv4-channels-contribute-to-renal-myogenic-autoregulation-in-neonatal-pigs
#19
Hitesh Soni, Dieniffer Peixoto-Neves, Anberitha T Matthews, Adebowale Adebiyi
Myogenic response, a phenomenon in which resistance size arteries and arterioles swiftly constrict or dilate in response to an acute elevation or reduction, respectively in intravascular pressure is a key component of renal autoregulation mechanisms. Although it is well-established that the renal system is functionally immature in neonates, mechanisms that regulate neonatal renal blood flow (RBF) remain poorly understood. In this study, we investigated the hypothesis that members of the transient receptor potential vanilloid (TRPV) channels are molecular components of renal myogenic constriction in newborns...
August 2, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28759041/oncosis-and-apoptosis-induction-by-activation-of-an-overexpressed-ion-channel-in-breast-cancer-cells
#20
A A Peters, S Y N Jamaludin, K T D S Yapa, S Chalmers, A P Wiegmans, H F Lim, M J G Milevskiy, I Azimi, F M Davis, K S Northwood, E Pera, D L Marcial, E Dray, N J Waterhouse, P J Cabot, T J Gonda, P A Kenny, M A Brown, K K Khanna, S J Roberts-Thomson, G R Monteith
The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype...
July 31, 2017: Oncogene
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